ABSTRACT The devastating effects of the COVID-19 pandemic have reverberated through every aspect of our civilization. While SARS-CoV-2, the viral etiology of COVID-19, seems to spare infants in terms of actual infection, it is currently unknown whether maternal infection during pregnancy will have long-term effects on children born during the pandemic. A variety of prenatal insults, including infections and stress, are well-known to lead to increased risk of affective disorders in both mother and child. With its disproportionate reach into already disadvantaged minority communities, the impact of the COVID-19 pandemic on the dyad is currently unknown and potentially of unprecedented magnitude with enduring consequences for women's mental health and children's developmental origins of health and disease (DOHaD). The COVID-19 Mother Baby Outcome (COMBO) initiative, a large multidisciplinary collaborative, was established at Columbia University Irving Medical Center to follow SARS-CoV-2 exposed laboring mothers and their newborns and compare their long- term health outcomes to case-matched dyads without prenatal exposure. This proposal will follow a subset of the larger COMBO cohort to study socioemotional circuits (fronto-limbic) and behavior (caregiving and bonding) in 100 mother-child dyads from prepartum to 18 months postpartum. The team assembled to carry out this study consists of two provider scientists (Dumitriu, pediatrician and neuroscientist, & Monk, clinical psychologist embedded in Ob/Gyn) and neuroscientist/pediatric neuroimager (Marsh). Using an innovative dyadic approach, olfaction testing, multimodal MRI, wearable in-home physiological recordings, observational mother and child assessments (free play, routine care, Harvard Reactivity and Still Face paradigms), this proposal will test the overarching hypothesis that prenatal SARS-CoV-2 exposure affects (1) mother and (2) child brain and behavior, and (3) demonstrate that the socioemotional health of each member of the mother- child dyad is intrinsically related to that of the other. Detecting COVID-19-related early neurobehavioral effects on mothers and the next generation will provide insights into intervention strategies and contribute significantly to DOHaD and stress science.

NARRATIVE The devastating effects of the COVID-19 pandemic have reverberated through every aspect of our civilization. While SARS-CoV-2, the viral etiology of COVID-19, seems to spare infants in terms of actual infection, it is currently unknown whether maternal infection during pregnancy will have long-term effects on children born during the pandemic. Detecting COVID-19-related early neurobehavioral effects on mothers and the next generation will provide insights into intervention strategies and contribute significantly to our understanding of children's developmental origins of health and disease and stress science in general.